Hemorrhagic fever with renal syndrome (HFRS) is a febrile disorder caused in Korea by the Hantaan and Seoul viruses. Its characteristic clinical manifestations include fever, hemorrhage, and renal failure, but a primary presentation with acute infectious diarrhea is rare. Owing to decreased urine output and renal function, a 54-year-old patient was transferred to our hospital from a local clinic, where he had been receiving treatment for diarrhea occurring more than 10 times a day. The patient was treated in the Gastroenterology Department at our hospital for acute renal failure secondary to inflammatory diarrhea based on the findings of stool leukocytes. An immunofluorescent antibody assay showed a 4-fold increase in the acute-phase antibody titer to Hantavirus during recovery. A nested reverse transcription polymerase chain reaction (RT-nPCR) assay of plasma yielded negative results, but Hantaan virus positivity was confirmed on an RT-nPCR assay of the buffy coat. Another 60-year-old patient with watery diarrhea was treated conservatively for suspected infectious diarrhea. However, an immunofluorescent antibody assay showed a 4-fold increase in the acute-phase HFRS antibody titer. RT-nPCR using plasma yielded negative results, but Seoul virus was detected on an RT-nPCR buffy coat assay, confirming the diagnosis of HFRS. Hemorrhagic fever with renal syndrome can present with gastrointestinal symptoms such as acute diarrhea alone. This report highlights the importance of considering HFRS in the differential diagnosis of patients with acute diarrhea and the need for additional research on the usefulness of the buffy coat in the PCR diagnosis of HFRS.